This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We propose a detailed investigation of the mechanism of conformational transition for three diverse proteins representing a signaling protein, an enzyme and a regulator through protein/protein interaction. Recent experiments conducted within our group on these three systems have shown that their ability of interconverting between different coexisting conformers is key to the accomplishment of their biological function. The goal of our investigations is to quantitatively model these conformational changes, and to understand at a molecular level the specific interactions most relevant in triggering and accompanying the interconversions. The proposed work is funded by the Dept of Energy (Award No. DE-FG02-05ER15699) and the Howard Hughes Medical Institute.